Abstract
Erectile dysfunction (ED), a prevalent disease among middle-aged and elderly males, significantly impacts both patient and partner quality of life. Phosphodiesterase type 5 inhibitor (PDE5i) represents an effective therapeutic method for ED. Given their widespread global utilization, concerns arise regarding potential reproduction-related problems arising from clinical use. During the extensive development of PDE5i, we speculated that the potential of these inhibitors to variably induce prostatic hyperplasia, but this field remains unexplored. In order to verify the male reproductive toxicity of PDE5i, sildenafil citrate at doses of 5, 10 and 20 mg/kg was administered in BPH model rats and aged rats. Anatomical and pathological analyses indicate a compelling association between sildenafil citrate administration and the promotion of prostatic hyperplasia in both BPH model rats and aged rats. Serum analyses revealed a notable increase in serum prostate binding protein (PBP) in BPH model rats following sildenafil citrate administration. Furthermore, significant increase in serum levels of E2 and T, as well as T in dorsal lobe prostate tissue of aged rats, were observed compared to the model control group. The epithelial-mesenchymal transition (EMT) microarray demonstrated that sildenafil citrate upregulated Fgfb1 and Tmeff1 within the EMT signaling pathway of the dorsal lobe prostate in BPH model rats, concurrently down-regulating Itga5, Versican and Vimentin. These results confirm the hypothesis that sildenafil citrate has reproductive toxicity in males and suggest that the EMT signaling pathway has a potential role in the proliferation of the dorsal lobe prostate in BPH model rats.